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Vascular dementia(VD) is a condition of cognitive impairment due to acute and chronic cerebral hypoperfusion. The available therapies for VD mainly focus on mitigating cerebral ischemia, improving cognitive function, and controlling mental behavior. Achievements have been made in the basic and clinical research on the treatment of VD with traditional Chinese medicine(TCM) active components, including Ginkgo leaf extract, puerarin, epimedium, tanshinone, and ginsenoside. Most of these components have anti-inflammatory, anti-apoptotic, anti-oxidant, and neuroprotective effects, and puerarin demonstrates excellent performance in mitigating cholinergic nervous system disorders and improving synaptic plasticity. Puerarin, ginkgetin, and epimedium are all flavonoids, while tanshinone is a diterpenoid. Puerariae Lobatae Radix, pungent in nature, can induce clear Yang to reach the cerebral orifices and has the wind medicine functions of ascending, dispersing, moving, and scurrying. Puerariae Lobatae Radix entering collaterals will dredge blood vessels to promote blood flow, and that entering the sweat pore will open the mind, which is in line with the TCM pathogenesis characteristics of VD. This study reviews the progress in the mechanism of puerarin, the main active component of Puerariae Lobatae Radix, in treating VD. Puerarin can ameliorate cholinergic nervous system disorders, reduce excitotoxicity, anti-inflammation, inhibit apoptosis, alleviate oxidative stress injury, enhance synaptic plasticity, up-regulate neuroprotective factor expression, promote cerebral circulation metabolism, and mitigate Aβ injury. The pathways of action include activating nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE), vascular endothelial growth factor(VEGF), extracellular regulated protein kinases(ERK), phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt), Janus-activating kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3), AMP-activated protein kinase(AMPK), as well as inhibiting the tumor necrosis factor α(TNF-α), transient receptor potential melastatin 2(TRPM2)/N-methyl-D-aspartate receptor(NMDAR), p38 mitogen-activated protein kinase(p38 MAPK), Toll-like receptor 4(TLR4)/nuclear factor-kappaB(NF-κB), early growth response 1(Egr-1), and matrix metalloproteinase 9(MMP-9). By reviewing the papers about the treatment of VD by puerarin published by CNKI, Wanfang, VIP, PubMed, and Web of Science in the last 10 years, this study aims to support the treatment and drug development for VD.
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Humanos , Demencia Vascular/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular , FN-kappa B/metabolismo , Antioxidantes , Isquemia Encefálica , ColinérgicosRESUMEN
Medicinal plants have a long history and play an important role in the prevention and treatment of human diseases. However, the interaction between bioactive components and specific biological targets in many medicinal plants is still unclear. Conventional separation and activity evaluation model of chemical constituents from natural products was time-consuming and laborious, and cannot truly reflect the interaction between the natural conformation of compounds and receptors, so these methods could not meet the urgent needs of modern drug development. Affinity ultrafiltration coupled with liquid chromatography-mass spectrometry (AUF-LC/MS) is a rapid, efficient and precise method focused on identification of bio-components from natural products, it can make up for many shortcomings found in conventional discovery of bio-constituents. However, AUF-LC/MS technology also has some drawbacks in experiments. In this paper, the principle, characteristics and application of AUF-LC/MS in the screening of active ingredients from medicinal plants are systematically reviewed, and its development prospect is prospected, so as to provide scientific basis for rapid and targeted screening of active components from medicinal plants.
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; Aim To observe the effects of CoQ10 on bone microstructure and myofibril structure induced by D-galactose in male mice. Methods Forty male mice were randomly divided into control group, model group, calcitriol group and CoQ10 group, in which drugs were given for 12 weeks. At the end of the experiment, the mice were sacrificed and the femurs were taken for micro-CT and biomechanics analysis. The gastrocnemius muscle was taken for transmission electron microscope examination. Results Compared with control group, the maximum load and stiffness of femur in model group significantly decreased (P < 0. 01). The micro-CT parameters showed that Conn. D and BMD markedly decreased (P < 0. 05), while Tb. Sp evidently increased (P <0. 05). In model group, the gastrocnemius muscle fibrils parameters showed that the length of sarcomere, I-band, H-zone, M-line and Z-line significantly increased (P < 0. 01), while the length of overlapped actin and myosin filaments significantly decreased (P < 0. 01) . Compared with model group, the maximum load, Conn. D., BMD and Tb. Th of femur in coenzyme Q 1 0 group markedly increased (P < 0. 05), while SMI and Tb. Sp significantly decreased (P < 0 . 01) . Moreover, I-band, H-zone, M-line and Z-line were significantly shortened (P < 0 . 01) . Conclusion Coenzyme Q10 can improve bone microstructure damage and the contractility of gastrocnemius muscle in male mice induced by D-galactose.
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As a unique innovative dosage form of China, traditional Chinese medicine injection (TCMI) has the characteristics of high bioavailability and rapid onset, therefore it plays an important role in the treatment of acute and severe diseases. However, more adverse reactions of TCMI have been reported along with its wide application in clinic and the increasing varieties. In the clinical application process, there are obvious color differences between the same kind of injection, which has attracted the attention of researchers whether this phenomenon is related to safety. The safety issue of TCMI has become more and more prominent, which greatly limits the application and development of TCMI. In this article, we summarized the reasons that influenced the chromatic aberration and safety of the TCMI, and analyzed the relationships between them. It is expected to provide some new ideas for exploring the reasons that affect the safety of TCMI and improving TCMI quality by technical improvement. This article provided a reference for rational application of TCMI in clinical practice.
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<p><b>OBJECTIVE</b>To investigate the neuro-protective effects of Acanthopanax senticosus Harms (EAS) on mesencephalic mitochondria and the mechanism of action, using a mouse model of Parkinson's disease (PD).</p><p><b>METHODS</b>The chemical fingerprint analysis of the extract of Acanthopanax senticosus Harms (EAS) was performed using the ultra performance liquid chromatograph and time of flight mass spectrometry. Thirty mice were randomly divided into the control group, the MPTP model group, and the EAS treated group with MPTP (MPTP+EAS group, 10 in each group). The MPTP model group and the MPTP+EAS group received MPTP-HCl (30 mg/kg i.p) once a day for 5 days. The control group received an equal volume of saline (20 mL/kg i.p) once a day for 5 days. Induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride daily (MPTP-HCl, 30 mg/kg) for 5 days, the PD mice were treated with EAS at 45.5 mg/kg daily for 20 days. The behavioral testing of mice was carried out using the pole-climbing test. The integrity and functions of neurons were examined in mesencephalic mitochondria in a PD mouse model, including nicotinamide adenine dinucleotide dehydrogenase ubiquinone flavoprotein 2 (NDUFV2), mitochondrially encoded nicotinamide adenine dinucleotide dehydrogenase 1 (MT-ND1), succinate dehydrogenase complex subunit A (SDHA), and succinate dehydrogenase cytochrome b560 subunit (SDHC).</p><p><b>RESULTS</b>After treatment with EAS, the behavioral changes induced by MPTP were attenuated significantly (P<0.05). EAS protected the mesencephalic mitochondria from swelling and attenuated the decreases in their membrane potential (both P<0.05), which was supported by an ultra-structural level analysis. The changes in reactive oxygen species (ROS), malonic dialdehyde (MDA), oxidative phosphorylation (OXPHOS) system 4 subunits levels and PD-related proteins expressions (parkin, Pink1, DJ-1, α-synuclein, and Lrrk2) reverted to near normal levels (all P<0.05), based on the results of immune-histological and Western blotting observations.</p><p><b>CONCLUSIONS</b>The neuro-protective effects of EAS are linked to protecting mice against MPTP-induced mitochondrial dysfunction and structural damage. Therefore, EAS is a promising candidate for the prevention or treatment of mitochondrial neurodegenerative disorders, such as PD.</p>
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Although multiple studies have shown that matrine can inhibit the proliferation of hepatoma cells, its mechanism of action has not been systematically investigated. In this study, the effects of matrine on the proliferation and migration of human hepatoma SMMC-7721 cells were investigated. Based on this result, anti-hepatoma target-functionally related protein interaction network of matrine was constructed, and topological analysis and clustering analysis were performed to predict the crucial targets of matrine for the anti-hepatoma effects. Pathway enrichment analysis was performed on the validated targets to predict the crucial pathways of matrine. Parts of the crucial proteins were examined by Western blot. Cellular experiments showed that matrine at concentrations of 1, 2 and 4 mg·mL-1 significantly inhibited the proliferation of SMMC-7721 cells, and matrine at concentrations of 0.5, 1 and 2 mg·mL-1 significantly inhibited the migration of SMMC-7721 cells. The results of network pharmacology suggest that matrine exerts its anti-hepatoma effects through acting on the key validated targets of heparanase (HPSE), caspase 3 (CASP3), Myc proto-oncogene protein (MYC), matrix metalloproteinases 2 (MMP2) and predicted targets of carbonic anhydrase 1 (CA1), lithostathine 1 alpha precursor (REG1A), carboxylesterases 1 (CES1) and acetaldehyde dehydrogenase 2 (ALDH2), and invasion and migration associated pathways. Western blot results suggest that matrine can down-regulate the expression of MMP2 and up-regulate the expression of CASP3. In this paper, we applied network pharmacology to explain the targets and pathways of matrine against hepatoma. The results provide a scientific basis for elucidation of the mechanisms of matrine against hepatoma.
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Objective To investigate the proliferation inhibitory effect of matrine in SMMC-7721 cells using 1H-NMR metabolomics approach. Methods CCK8 method was used to detect the proliferation inhibitory effect of matrine in SMMC-7721 cells, and the cell lysates and cell culture supernatants were detected by 1H-NMR combined with multivariate statistical analysis and metabolic pathway analysis with the aim of exploring its mechanism of action. Results Matrine at the concentration of 1, 2, and 4 mg/mL could significantly inhibit the proliferation of SMMC-7721 cells. Compared with control group, 21 differential metabolites were confirmed inside and outside the cells after treatment of matrine. Matrine could significantly regulate the contents of differential metabolites such as leucine, valine and glycine inside and outside the cells, and regulate the amino acid metabolism of hepatoma cells. Conclusion Matrine plays anti-hepatoma effect likely through regulation of amino acid metabolism and energy metabolism. This study provides a scientific basis for elucidation of the anti-hepatoma mechanism of matrine from the perspective of metabolomics.
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Objective: To explore the intervention of baicalein on D-galactose-induced aging rats by 1H-NMR metabonomics methods. Methods: The aging model was induced by sc injection of D-galactose (150 mg/kg) in rats, and the effects of baicalein (50, 100, and 200 mg/kg) on autonomic activities of aging rats were investigated. After 10 weeks, the serum of rats was collected for 1H-NMR detection, and the anti-aging effects of baicalein were explored using multivariate statistical analysis. Results: Baicalein significantly improved the locomotor activities of aging rats. Compared with control group, the levels of alanine, acetic acid, pyruvic acid, tyrosine, and N-acetyl glycoproteins in rat serum of model group increased, while the levels of glutamine, dimethyl glycine, glycine, threonine, creatinine, and histidine decreased. These 11 potential biomarkers could be reversely regulated after treatment with baicalein. Conclusion: Baicalein exerts anti-aging effects likely through regulation of amino acid metabolism, nucleotide metabolism, and glucose metabolism.
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In order to explore the anti-aging effect of baicalein, female Drosophila melanogaster as a model organism was used to study the effects of baicalein on natural aging model and aging models induced by hydrogen peroxide (H2O2) and paraquat. The bioinformatics approach was used to predict the possible target for the anti-aging activity of baicalein, and the target pathways were identified. The oxidative stress pathway was a focus in experiment. Baicalein at concentrations of 0.04 mg·mL-1 and 0.2 mg·mL-1 extended the mean and maximum lifespans in the natural aging model, and effectively reduced the damages of oxidative stress by H2O2 and paraquat. 31 senescence-related targets together with the oxidative stress pathway were modulated by baicalein. The experiments revealed that baicalein might delay aging process through attenuation of the oxidative stress response by decreasing the reactive oxygen species (ROS), malondialdehyde (MDA) and oxidized glutathione (GSSG) in Drosophila melanogaster.
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<p><b>BACKGROUND</b>Loss of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) expression is an adverse prognostic factor in hepatocellular carcinoma (HCC). The purpose of this study was to investigate the expression of CEACAM1 and its effect on relapse-free survival (RFS) following liver transplantation (LT) for HCC.</p><p><b>METHODS</b>Expression of CEACAM1 was immunohistochemically detected in HCC specimens from 48 patients. The relationship between CEACAM1 expression and clinicopathologic variables, as well as tumor recurrence, was further analyzed.</p><p><b>RESULTS</b>Of the 48 HCC specimens, membranous CEACAM1 expression was detected in 25 specimens and cytoplasmic CEACAM1 expression was detected in 19 specimens. Four specimens had loss of CEACAM1 expression. Loss of membranous CEACAM1 expression was significantly associated with tumor size, tumor number, and serum α-fetoprotein levels (all P < 0.05). Patients with loss of membranous CEACAM1 had significantly poorer RFS than patients with membranous expression, determined via Kaplan-Meier analysis (P = 0.027). Multivariate analysis revealed that loss of membranous CEACAM1 expression might be an independent prognostic factor of RFS for HCC patients after liver transplantation (P = 0.037).</p><p><b>CONCLUSION</b>Loss of membranous CEACAM1 expression in HCC was closely associated with aggressive tumor biology and might be a relapsing biomarker of HCC treated with LT.</p>
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Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antígenos CD , Metabolismo , Carcinoma Hepatocelular , Metabolismo , Mortalidad , Cirugía General , Moléculas de Adhesión Celular , Metabolismo , Inmunohistoquímica , Estimación de Kaplan-Meier , Neoplasias Hepáticas , Metabolismo , Mortalidad , Cirugía General , Trasplante de HígadoRESUMEN
<p><b>BACKGROUND</b>Ischaemic reperfusion injury (IRI) is inevitable during major liver surgery. Ischaemic preconditioning (IPC) has been proven an effective intervention against hepatic IRI. Recently, it was demonstrated that ischaemic postconditioning (IPO) provided effective cardioprotection on IRI. We evaluated the protective effects of IPO on warm/cold IRI in rat liver by a comparison with IPC and assessed the role of apoptosis in the process.</p><p><b>METHODS</b>Warm IRI model (clamping hepatic pedicle for 30 minutes) and cold IRI model (orthotopic liver transplantation with 2 hours cold storage) were established. Each model consisted of 3 groups: (1) control group, normal warm/cold IRI; (2) IPC group, 5 minutes of ischaemia followed by 5 minutes of reperfusion twice prior to warm/cold IRI; (3) IPO group, 30 seconds of reperfusion followed by 30 seconds of reocclusion for three times after warm/cold ischaemia. The levels of serum transaminase, glucose, and gamma glutamyltransferase (GGT) in bile, histopathological examination, apoptotic activity of hepatocyte, and apoptosis related protein Fas, at 3 hours after operation were compared. Survival rates one week after intervention were also compared.</p><p><b>RESULTS</b>IPO and IPC protected the functions of hepatocytes and biliary epithelial cells, inhibited the hepatocellular apoptosis by preventing expression of Fas gene, and elevated the one week survival rate compared with control group in both models (P < 0.05). IPO and IPC groups were comparable in levels of serum transaminase levels, glucose, and GGT in bile, Fas positive expression index, and one week survival. In cold ischaemic models, IPO had lower apoptotic index than IPC (P < 0.05).</p><p><b>CONCLUSION</b>Compared with ischaemic preconditioning, ischaemic postconditioning is associated with comparable protections of rat liver from warm or cold ischaemic reperfusion injury.</p>
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Animales , Masculino , Ratas , Apoptosis , Precondicionamiento Isquémico , Hígado , Patología , Ratas Wistar , Daño por Reperfusión , Tasa de Supervivencia , Receptor fas , GenéticaRESUMEN
<p><b>OBJECTIVE</b>To summarize the experience of laparoscopic common bile duct exploration.</p><p><b>METHODS</b>The clinical data of 587 cases who underwent laparoscopic common bile duct exploration from June 1992 to May 2006 were analyzed.</p><p><b>RESULTS</b>The surgery was successful in 585 cases (99.7%), 2 cases were converted to open common bile duct exploration. The duration of operation was 60 approximately 230 min (averaged 85 min), the complications consisted of biliary fistula (n=13), injury of the duodenum (n=1), abscess of drainage tube orifice (n=1), titanium clip discharging out from T tube (n=3), residual common bile duct stones (n=35). The patients could take food and walk on the second postoperative day and average postoperative hospital stay was 4.6 days.</p><p><b>CONCLUSIONS</b>Laparoscopic common bile duct exploration is a safe and effective procedure in treating the calculus of bile duct.</p>
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Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de las Vías Biliares , Cirugía General , Procedimientos Quirúrgicos del Sistema Biliar , Métodos , Conducto Colédoco , Cirugía General , Laparoscopía , Complicaciones Posoperatorias , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
<p><b>BACKGROUND</b>Laparoscopic splenectomy (LS) has been considered as the standard approach to remove a normal-sized spleen, but it is facing technical challenges when applied to splenomegaly. Hand-assisted laparoscopic technique was designed to facilitate the performance of difficult laparoscopic procedure. This study was aimed to evaluate the efficacy and superiority of hand-assisted laparoscopic splenectomy (HALS) for splenomegaly.</p><p><b>METHODS</b>From November 1994 to January 2006, 36 patients with splenomegaly (final spleen weight > 700 g) were treated with laparoscopic operations for splenectomy in our hospital. Conventional LS was performed in 16 patients (7 men and 9 women, group 1) and HALS in the other 20 patients (12 men and 8 women, group 2). The patients' features, intraoperative details and the postoperative outcomes in the both groups were compared.</p><p><b>RESULTS</b>The both groups were comparable in the terms of patient's age ((38 +/- 12) years vs (43 +/- 14)years, P > 0.05), the greatest splenic diameter ((24 +/- 5)cm vs (27 +/- 7)cm, P > 0.05), preoperative platelet count ((118 +/- 94) x 10(9)/L vs (97 +/- 81) x 10(9)/L, P > 0.05) and diagnosis. Compared with LS group, operation time ((195 +/- 71) minutes vs (141 +/- 64) minutes, P < 0.05) was shorter, intraoperative blood loss ((138 +/- 80)ml vs (86 +/- 45)ml, P < 0.05) and conversion rate (4/16 vs 0/20, P < 0.05) were lower, but hospital stay ((5.3 +/- 3.8) days vs (7.4 +/- 1.6) days, P < 0.05) was longer in HALS group. There was no significant difference in the aspects of intraoperative and postoperative complication rate (2/16 vs 0/20, P > 0.05) or recovery time of gastrointestinal function ((16.3 +/- 11.6) hours vs (18.7 +/- 8.1) hours, P > 0.05) between the two groups.</p><p><b>CONCLUSIONS</b>In the cases of splenomegaly, HALS significantly facilitates the surgical procedure and reduces the operational risk, while maintaining the advantages of conventional LS. HALS is more feasible and more effective than conventional LS for the removal of splenomegaly.</p>
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Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Laparoscopía , Métodos , Esplenectomía , Métodos , Esplenomegalia , Cirugía GeneralRESUMEN
<p><b>BACKGROUND</b>Stem cells, which have the ability to differentiate into insulin-producing cells (IPCs), would provide a potentially unlimited source of islet cells for transplantation and alleviate the major limitations of availability and allogeneic rejection. Therefore, the utilization of stem cells is becoming the most promising therapy for diabetes mellitus (DM). Here, we studied the differentiation capacity of the diabetic patient's bone marrow-derived mesenchymal stem cells (MSCs) and tested the feasibility of using MSCs for beta-cell replacement.</p><p><b>METHODS</b>Bone marrow-derived MSCs were obtained from 10 DM patients (5 type 1 DM and 5 type 2 DM) and induced to IPCs under a three-stage protocol. Representative cell surface antigen expression profiles of MSCs were analysed by flow cytometric analysis. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect multiple genes related to pancreatic beta-cell development and function. The identity of the IPCs was illustrated by the analysis of morphology, ditizone staining and immunocytochemistry. Release of insulin by these cells was confirmed by immunoradioassay.</p><p><b>RESULTS</b>Flow cytometric analysis of MSCs at passage 3 showed that these cells expressed high levels of CD29 (98.28%), CD44 (99.56%) and CD106 (98.34%). Typical islet-like cell clusters were observed at the end of the protocol (18 days). Ditizone staining and immunohistochemistry for insulin were both positive. These differentiated cells at stage 2 (10 days) expressed nestin, pancreatic duodenal homeobox-1 (PDX-1), Neurogenin3, Pax4, insulin, glucagon, but at stage 3 (18 days) we observed the high expression of PDX-1, insulin, glucagon. Insulin was secreted by these cells in response to different concentrations of glucose stimulation in a regulated manner (P<0.05).</p><p><b>CONCLUSIONS</b>Bone marrow-derived MSCs from DM patients can differentiate into functional IPCs under certain conditions in vitro. Using diabetic patient's own bone marrow-derived MSCs as a source of autologous IPCs for beta-cell replacement would be feasible.</p>